Table 2 Sex differences in opioid consumption and cue reactivity.

ARSW, Adjective Rating Scale for Withdrawal; COWS, Clinical Opiate Withdrawal Scale; VAS, visual analog scale; M, male; F, female.

SubjectsBehavioral measureSex differences
HumanPrevalence of heroin or prescription opioid useM > F
F > M increased rate of heroin use
Rate of increased/decreased heroin or prescription
opioid use across years (2007–2014)
F < M decreased rate of prescription opioid
use (12)
Human; heroin-dependent, in-patient settingSelf-reported craving and physiological measures
after viewing: heroin-related imagery
F > M self-reported cravings and sadness, systolic
blood pressure, heart rate
Heroin paraphernaliaF > M diastolic blood pressure, self-reported
decreased joy
M > F self-reported anger (14)
Human; opioid-dependent, buprenorphine
tapering clinical trial
Self- and clinician-reported withdrawal symptoms
(ARSW, COWS) and craving (VAS)
F > M withdrawal symptoms (ARSW, COWS) and
subjective craving (VAS) (15)
Human; healthy volunteersSelf-reported drug effects questionnaire after
intramuscular morphine administration
M > F self-reported positives effects and drug
F > M self-reported negative subjective effects (72)
Human; opioid-dependent, methadone- or
Self-reported craving and mood using ecological
momentary assessment
F > M self-reported craving for opioids as a
function of stress severity
F > M self-reported craving for opioids in presence
of stress and cues (73)
Human; opioid-dependent, morphine-stabilized, in
opioid tapering clinical trial
COWS and self-reported withdrawal ratings after
intramuscular naloxone injection
More F in high withdrawal phenotype than low
M = F in naloxone-precipitated withdrawal
scores (78)
Mouse; 1 or 6 hours for intravenous heroinSelf-administrationF > M self-administered heroin
Somatic signs of withdrawalF = M somatic withdrawal signs (22)
Mouse; 1 or 12 hours for fentanyl vaporFentanyl intake during transition from short
(1 hour) to long (12 hours) access
F > M intake in the first three sessions
Escalation across 10 days of 12-hour accessM > F change in intake (escalation slope)
across days
Naloxone-precipitated withdrawalF > M somatic signs of withdrawal (23)
Rat; 6-hour session for intravenous heroinDays to acquisition criteriaF > M rate of acquisition (faster to acquire)
Infusions per sessionF = M total intake during acquisition (83)
Rat; 4-hour sessions for intravenous heroinInfusions per sessionF > M infusions at 1.25 or 3.75 μg per infusion
F = M infusions at 15–30 μg per infusion (84)
Rat; 1-hour session for oral oxycodoneIntake across dosesF > M mg/kg intake at 1.0 mg/ml
Naloxone-precipitated intakeF > M intake after naloxone injection
Progressive ratioF = M breakpoint
Stress-primed reinstatementF = M active lever presses (85)
Rat; 2-hour session for intravenous fentanylIntake across dosesF > M infusions at 0.32–1 μg/kg dose
Motivation (demand curve)F > M demand/essential value at 10 μg/kg per
infusion (not 3.2 μg/kg per infusion)
F = M baseline consumption (87)
Rat; 6-hour session for intravenous oxycodoneBuprenorphine effect on reinstatementBuprenorphine reduced reinstatement in F but
not in M
Buprenorphine effect on reacquisition of
Buprenorphine reduced reacquisition in F
and M (89)
Rat; 6-hour session for intravenous heroinIncubation of heroin craving after forced
F and M incubated craving (increased responding)
between abstinence days 1 and 21
No incubation of craving between abstinence
days 1 and 21 in F or M (88)
Mouse; 3-hour session for oral oxycodoneIntake across dosesF > M mg/kg intake at the 0.30–1 mg/kg dose
Cue-induced reinstatementF = M (86)